Patients with lung cancer, colorectal cancer and esophageal cancer experience multiple severe symptoms related to aggressive cancer treatment. Typically these symptoms occur together. Some of the most prevalent of these symptoms, especially cancer-related fatigue, are very difficult to treat and are a major source of distress for patients as well as families. Development of new methods for treating or preventing these symptoms, especially treatments with minimal side effects, is a high priority, but depends on a better understanding of the mechanisms responsible for symptom expression. Previous human and animal studies suggest that high serum levels of cytokines might be one mechanism underlying multiple symptoms (Cleeland, et al, 2003). Interleukin (IL)-6, for example, is known to be elevated in lung and colorectal cancer and to decrease in response to treatment. We propose a study to longitudinally assess the symptoms and the serum levels of a panel of cytokines (IL-1RA, IL-6, IL-8, EL-10, LL-12, and TNF-alpha) in patients with stage TTR or ETI lung, colorectal and esophageal cancer who are undergoing chemoradiation therapy, to (1) characterize the relationship between IL-6 and symptoms over the time of treatment and (2) identify related cytokine(s) (focusing on IL-6) as indicators of high risk for severe fatigue and other symptoms that develop during therapy. This study will use a novel server-based (interactive voice response) assessment of symptoms on a weekly basis using the M.D. Anderson Symptom Inventory, hi three or four minutes, patients can use their home phones or phones in hospital rooms to rate their symptoms and symptom-related interference. Cytokine sample will be collected before therapy, weekly clinic visit during therapy and at one-month post therapy. Longitudinal methods, such as mixed effect modeling, will be used to assess the strength and nature of the relationship between cytokines and symptoms. These pilot studies may lead to additional multi-disciplinary animal and clinical studies of the mechanisms underlying disease-related and treatment-related cancer symptoms.